Research ArticleCancer

T cell–induced CSF1 promotes melanoma resistance to PD1 blockade

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Science Translational Medicine  11 Apr 2018:
Vol. 10, Issue 436, eaan3311
DOI: 10.1126/scitranslmed.aan3311

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CSF1 curbs immunotherapy efficacy in melanoma

Although melanoma is one of the cancer types best targeted by checkpoint blockade, many patients are refractory to therapy. One likely culprit is the persistence of tumor-associated macrophages, which can be immunosuppressive. Neubert and colleagues examined patient samples and performed coculture experiments that implicated CD8+ T cell induction of tumor-derived CSF1, which could then promote immunosuppressive macrophages. Addition of CSF1 signaling blockade to anti-PD1 treatment improved responses in transplantable mouse melanoma models. These results uncover the biology of hurdles that still need to be overcome in immunotherapy, and also suggest a solution.